The goal of this project is to assess multiple factors related to the pathogenesis of neurological diseases. The research is focused on the investigation of multiple sclerosis (MS). Genetic and immunological factors which may contribute to this disorder are being evaluated in patients with sporadic disease and families with multiple affected members. Genes encoding HLA molecules and T-cell receptors in normal controls and individuals with MS are being compared. The cellular immune responses to myelin basic protein, proteolipid protein, and common human viruses are being evaluated in the same populations. Patients with other inflammatory disorders of the central nervous system that resemble MS are being assessed. These include, systemic lupus erythematous, other forms of vasculitis, and HTLV-I-associated myelopathy/tropical spastic paraplegia (HAM/TSP). Immunologic, clinical, and MRI findings in HAM/TSP are being compared to normal carriers of HTLV-I. Evidence of an immunopathologic component to HAM/TSP has been obtained from the detection of high levels of cytotoxic lymphocytes directed at HTLV-I in the blood. New approaches have been developed to assess cellular immune activity in the cerebrospinal fluid. Patients who have high levels of cytotoxic T cells directed at HTLV-I are being treated with a high-dose, alternate-day steroid regimen. Neurologic disorders associated with HTLV-II are being assessed, as well as normal carriers of this virus.